1. Field of the Invention
This invention relates in general to mass spectrometers, and in particular to pulsed ion sources for mass spectrometers.
2. Background of the Invention
Mass spectrometry is an analytical technique used to measure the mass of ionized chemical species by separating ions according to their mass-to-charge ratios, and detecting ions in an ion detector. Ionization of chemical samples for mass analysis can be accomplished by a variety of methods including for example atmospheric pressure matrix-assisted laser desorption ionization (AP-MALDI), electrospray ionization, atmospheric pressure chemical ionization (APCI), inductively-coupled plasma (ICP) discharge, and photoionization. The generated ions are transmitted through an atmospheric pressure inlet into a lower vacuum region where ion guides direct the ions into a mass detector.
In atmospheric pressure ion sources, ions (or charged species like small liquid droplets as in the case of electrospray ionization) are dispersed once created. Dispersion of the created ions makes efficient sampling of ions from atmospheric pressure sources difficult. Atmospheric pressure inlets are typically a small aperture or capillary of a limited cross section. Consequently, a significant portion of ions that are created are typically unable to pass through the aperture and are lost for mass analysis. Efficient transport of ions through a small aperture or capillary is even more challenging when the ions are generated farther removed from a region directly adjacent to the aperture. For high sensitivity and high throughput mass analysis, it is important to minimize ion losses before the ions reach a mass detector.
One approach for sampling ions from an atmospheric pressure source is to create ions on-axis with a mass spectrometer""s sampling aperture/tube. However, this approach requires precise aperture alignment and source positioning. Furthermore, even using precise procedures, the sampling efficiency is generally less than 1 ion in 104. In AP-MALDI, described by Laiko et al. in U.S. Pat. No. 5,965,884 and in Anal. Chem. 2000 (vol. 72, pp. 652-657, vol. 72, pp. 5239-5243), the entire contents of which are incorporated by reference, a laser irradiation pulse is used to create ions. Ions created with AP-MALDI are extracted into an atmospheric pressure inlet of a mass spectrometer with the aid of both a static electric field and the intake gas flow into the mass spectrometer. In an AP-MALDI configuration, positioning of the laser beam directly on-axis with the aperture provides the best sensitivity. However, a significant fraction of ions are still lost to the walls of the mass spectrometer inlet during the on-axis, continuous extraction procedure. U.S. Pat. No. 4,209,696, the entire contents of which are incorporated by reference, describes combining electrospray ionization sources with pinhole apertures which is yet another example of inefficient ion sampling requiring high precision aperture alignment and source placement.
Still another approach has been to focus ions into a sampling aperture as described in Smith et al. U.S. Pat. No. 6,107,628, the entire contents of which are incorporated by reference. Smith et al. describe an ion funnel that consists of a series of elements of decreasing size. Radio frequency (RF) voltages are applied to alternating elements to direct ions. Franzen, (U.S. Pat. No. 5,747,799), the entire contents of which are incorporated by reference, describe focusing with a plate lens placed in front of an aperture plate. Fenn et al., (U.S. Pat. No. 4,542,293), the entire contents of which are incorporated by reference, describe focusing with a plate lens placed in front of a capillary. In addition, mass spectrometer entrances have utilized conical skimmer apertures to improve ion collection efficiency over planar apertures. But this approach is limited by the acceptance angle of the static electric field generated by the cone. In addition, source position is once again critical to performance.
All these focusing devices are inherently complex, position dependent, and not efficient. Consequently there exists a need for a device to increase the ion sampling efficiency of ion sources.
One object of the present invention is to increase the sensitivity and detection limits of an ionic species generated external to a mass spectrometer.
A further object of this invention is to increase ion transmission through an atmospheric pressure inlet of a mass spectrometer.
Still, a further object is to provide a technique by which laser spot alignment with an axis of a mass analyzer is not critical to ion collection.
Yet, another object is to provide ion collection from laser-irradiated areas larger than an aperture diameter entrance of a mass analyzer.
These and other objects are accomplished, according to the present invention, in an apparatus and a method which produce a pulse of ions, generate a transient electric field correlated in time with a duration of the pulse of ions, receive the pulse of ions into the transient electric field, and collect the ions from an ion drift region of the transient electric field into a gas dynamic flow region of the mass analyzer. As such, an apparatus for transferring ions into a mass analyzer includes an ion source configured to generate the pulse of ions, a transient electric field device configured to receive the pulse of ions and generate the transient electric field, and an ion collector configured to collect the ions from the ion drift region and transfer the ions into the mass analyzer.
In one aspect of the present invention, the apparatus includes an AP-MALDI ion source, switching circuitry, and a timing device which creates a transient high-voltage (HV) extraction field. Ions in an AP-MALDI ion source are generated by a pulsed laser. The laser pulse is generated prior to the onset of a transient high-voltage extraction field. According to the present invention, the transient high-voltage extraction field is maintained for a set time interval after the laser pulse and then removed thereafter. The result of which is an increased transmission of ions into the mass analyzer inlet. Because the HV extraction field is no longer static and continuous, but rather applied for a limited initial time period after the pulse of ions is formed, the term xe2x80x9ctimed-extractionxe2x80x9d is used herein to describe a number of ways in which the transient high-voltage extraction field is utilized in relation to pulse ion generation.
In conventional ion collection, ions drift in the applied static electric field from the target to the MS instrument entrance orifice. As a result, some of the ions from the ion source reach the orifice and are then delivered to a mass analyzer region, but many of the ions impact the metal areas surrounding the entrance to the mass analyzer (typically a capillary or a cone wall) and are neutralized and lost from the mass analysis.
In the present invention, the static electric field used conventionally is replaced by a transient electric field which, for example can be applied after generation of a pulse of ions. Ions drift in the transient electric field toward the entrance of the mass analyzer. At a moment, prior to reaching the entrance, the transient electric field is terminated or at least reduced. Since the drift velocity of ions due to the electric field is directly proportional to the electric field strength, the ions do not impact the walls as severely as would occur if the electric field continued to exist. Further, the motion of the ions after termination of the transient electric field is governed by gas dynamics of the gas flow entering the mass analyzer (i.e. a gas dynamic flow region of the mass analyzer) which dominates transport mechanisms in the vicinity of the entrance to the mass analyzer, especially in the absence of an electric field. As a result, ions are not lost on the wall and more ions are entrained in the gas flow of the gas dynamic region and collected into the mass analyzer. Thus, the xe2x80x9cturning offxe2x80x9d of the field after ions arrive in a region where the gas dynamic flow is substantial results in alleviating the loss of ions from the gas phase due to impact of the ions on the metal walls and neutralization.
One feature of the present invention is that it not only allows ions directly on axis with the mass spectrometer inlet to be analyzed, but by permitting ion drifting in the transient electric field also increases the collection efficiency for ions generated off-axis. This feature, according to the present invention, accommodates laser position fluctuations in atmospheric pressure ion sources such as MALDI without degradation of ion transmission into the mass analyzer. Furthermore, this feature, according to the present invention, allows different laser positions, sizes and energies, along with different target plate-to-MS inlet configurations to be used advantageously to improve ion throughput.